Mutational Analyses Of The TSC1 And TSC2 Genes In Cases Of Tuberous Sclerosis Complex

Background Tuberous sclerosis complex?TSC?is an autosomal dominant genetic disease characterized by hamartomas in multiple organ systems,including the brain,skin,heart,kidneys,and lung.Facial angiofibromas,seizures and mental retardation are the three common clinical manifestations of TSC.The pathogenic genes are TSC1 and TSC2 and both indicated as tumour-suppressor genes.In recent years,many TSC mutation sites have been found in Chinese Han patients with TSC.However,there are no obvious hot spot mutation.In addition,the relationship between TSC genotype and phenotype remains unclear.Aim The study was designed to identify pathogenic TSC1 or TSC2 gene mutations in one family and two sporadics.In addition,the study reviewed the data of TSC mutations and clinical features to investigate the correlations between genotype and phenotype in Chinese TSC patients.Methods Mutational analyses of TSC1 and TSC2 gene was performed in one familial and two sporadic cases with Sanger squencing and TA cloning.By reviewing literatures,we performed the correlations between genotype and phenotype by paired chi-square tests.Results 1.The study identified one novel mtation?c.1884₁887del AAAG?and one reported mutation?c.1960G>C?in family 1 with Sanger squencing.The result of TA cloning was that the two mutations were on the same alleles.2.The study identified one novel mutation?c.5266A> G?and one reported mutation?c.4258₄261del TCAG?.The two mutations both could lead to the changes of amino acid and were predicted to be pathogenic.3.Our literature review showed that TSC2 gene mutations were more frequent than TSC1 gene mutations.Patients with TSC2 mutations had a higher frequency of mental retardation??2=8.139?P=0.004?and familial inheritance??2=17.489?P<0.05?than TSC2 gene mutations.There was no significant difference in the frequent of skin lesions and seizures.Conclusions The identification of the TSC1/TSC2 gene mutations confirmed the diagnosis of the 3 patients with TSC.There were two frameshift mutations and two missense mutations?including one non-pathogenic mutation?.In addition,we conducted a statistical analysis between TSC genotypes and phenotypes that the frequency of TSC2 mutations was more than that of TSC1 mutations and clinical manifestations were more serious.Furthermore,the founding expanded the spectrum of TSC gene mutations and explained the molecular pathologic mechanisms causing TSC.Meanwhile,It could guide individualized treatment and prognostic assessment of patients with TSC...